Personality traits are summarized by five broad dimensions with pervasive influences on major life outcomes, strong links to psychiatric disorders and clear heritable components. To identify genetic variants associated with personality traits we perform genome-wide association studies(GWAS) on a genetically isolated population within Sardinia, Italy. In the first study of the five major dimensions of personality the analyses of 362129 single nucleotide polymorphisms (SNPs) revelead several strong signals within or near genes previously implicated in psychiatric disorders. They include the association of neuroticism with SNAP25, extraversion with BDNF and two cadherin genes (CDH13 and CDH23), openness with CNTNAP2, agreeableness with CLOCK, and conscientiousness with DYRK1A. Effect sizes were small (less than 1% of variance), and most failed to replicate in the follow-up independent samples (N up to 3903), though the association between agreeableness and CLOCK was supported in two of three replication samples. We infer that a large number of loci may influence personality traits and disorders, requiring larger sample sizes for the GWAS approach to confidently identify associated genetic variants.